Rare diseases (RDs) or orphan diseases, by definition, are conditions that affect a small number of individuals. The exact number of RDs is unknown, but it is estimated to be approximately 6000-8000.

Although each individual disease is rare, their collective prevalence is estimated at around 6%-8% of the population. This implies that over 450 million persons worldwide may have an RD. In addition, although heterogeneous in causes and manifestations, most RDs are chronic and debilitating and are a substantial cause for disability and early death. They manifest as congenital anomalies, intellectual disabilities, and many other severe signs and symptoms. Most lack curative therapies. They constitute a substantial cause of health-care spending for individuals and society and also have indirect economic impact due to loss of productivity. For these reasons, RDs constitute a relevant and global public health-care problem.

FDA support for orphan drug development programs

Supporting the development and evaluation of new treatments for rare diseases is a key priority for the FDA. The FDA has authority to grant orphan-drug designation to a drug or biological product to prevent, diagnose or treat a rare disease or condition. Orphan drug designation qualifies sponsors for incentives including: Tax credits for qualified clinical trials, Exemption from user fees, Potential 7 years of market exclusivity after approval

Orphan Drug Development challenges

Orphan drug development presents several major challenges and obstacles, such as low disease prevalence, disease severity, small and heterogeneous patient populations, difficulties in patient recruitment, and limited knowledge of the natural history of disease, among others. Rare diseases that affect limited patient populations and have not been extensively studied can pose significant research and development challenges for companies looking to identify new drugs to treat them. In a recent Tufts Center for the Study of Drug Development survey, rare drug developers indicated that they must overcome many different types of challenges owing to the lack of knowledge about disease mechanisms. In addition to an incomplete understanding of the biology underlying these diseases, researchers often do not have information about their natural history and are uncertain how to translate what information has been gathered into useful knowledge for drug development. In addition, they may have to choose between multiple potential disease pathways and establish endpoints and outcome measures

Strategies for Orphan Drug Development

Several strategies can be used to plan for and overcome these clinical and regulatory challenges, namely improved clinical trial design, improved patient recruitment, and closer collaboration with the regulatory authorities and with patient associations.

In orphan drug development, efficient study designs with appropriate comparators are key to generating interpretable clinical data for approval. Designing efficient clinical trials with clinically meaningful endpoints, however, requires close collaboration among statisticians, clinicians, and other clinical trial professionals, and a strong focus on patient needs.

Regulatory Approvals

A rare disease drug may be approved based on just one appropriately controlled trial as long as the trial provides sufficient evidence and safety information to allow for benefit/risk assessments. In some cases, the FDA even accepts non-traditional data on treatment effectiveness.

Manohara Halasiddappa

Clinical Operations Leader, San Francisco